Primary Malignant Tumors Research Articles

Comparison of miRNA Profiles of Primary Tumors and Metastatic Tumors of Salivary Gland Tumors and Their Role in Prognosis: A Systematic Review.

MicroRNAs (miRNAs) are implicated in several biological processes, such as control of tissue homeostasis, cell signaling, differentiation, proliferation, neoplastic transformation, and activation/inhibition of apoptotic mechanisms. In this systematic review, we evaluated the changes in the expression pattern of miRNAs in salivary gland tumors (SGTs). A comprehensive search was conducted in PubMed, and Scopus with no language and date restrictions in Feb 2023. All the studies on SGTs that evaluated miRNA profiling were included. Relevant data regarding the overexpression and down-regulation of the miRNAs were extracted. The quality of the included studies was evaluated with Newcastle-Ottawa checklist. The altered expression of miRNAs was evaluated between SGTs and normal cases, benign and malignant tumors, and primary and high-grade tumors. Thirteen studies were included in this systematic review. There were considerable differences between malignant and benign tumors regarding the miRNAs expression level. In the five studies, the miRNA profile of the primary tumors was compared with metastatic tumors to reveal the involvement of the miRNA in the prognosis of the salivary tumors. The miRNAs expression changes were correlated with tumor size, stage, recurrence, and occurrence of solid components. Perineural invasion and lymph node metastasis were also reported in ACCLM cell line and recurrence of adenoid cystic carcinoma (ACC) tissues. The miRNA profiling confirms their prognostic value in salivary gland tumors. Significant alternations of the miRNAs expression are useful for distinguishing different types of salivary tumors and malignant tumors from benign types. The miRNA expression changes also affect the prognosis of salivary tumors.

GNAS, not a Highly Mutated Gene, Has Prognostic Significance and Carcinogenic Effects in Osteosarcoma.

Osteosarcoma is a prevalent and aggressive primary malignant bone tumor affecting children and adolescents. Despite advancements in sequencing technologies, there remains a lack of reliable prognostic biomarkers and effective targeted therapies for osteosarcoma. This study focuses on identifying key prognostic genes, particularly the role of GNAS, in osteosarcoma progression. Bioinformatics analyses were performed on osteosarcoma datasets from the Gene Expression Omnibus (GEO). Differential gene expression analysis, weighted correlation network analysis (WGCNA), and survival analysis identified potential prognostic hub genes. The expression and function of these genes were validated through immunohistochemistry and animal experiments. Specifically, the role of GNAS was investigated through siRNA-mediated knockdown in osteosarcoma cell lines and nude mice models. Five hub genes (PROP1, GNAS, CYP4F2, LHX3, CNGB1) were identified as significantly related to osteosarcoma prognosis. Among these, GNAS was found to be highly expressed in osteosarcoma tissues compared to normal tissues. Immunohistochemical analysis confirmed the elevated expression of GNAS in osteosarcoma samples. GNAS mutation analysis revealed a low mutation rate in osteosarcoma, suggesting its oncogenic role is independent of mutational status. Animal experiments demonstrated that knocking down GNAS significantly inhibited tumor growth and induced apoptosis in osteosarcoma cells. GNAS is highly expressed in osteosarcoma and associated with poor prognosis, acting as an oncogene in osteosarcoma progression. Targeting GNAS could be a potential therapeutic strategy for osteosarcoma. Further studies on GNAS-related signaling pathways may provide deeper insights into the molecular mechanisms driving osteosarcoma malignancy.

Patterns and Clinicopathological Features of Histologically Proven Metastases in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver malignant neoplasm. Multiple risk factors have been identified for several decades for this overly aggressive tumor. HCC is an overly aggressive malignancy with frequent intrahepatic and extrahepatic metastasis. In our practice, we have observed that HCC has the propensity to metastasize to very unusual sites and can sometimes show variable patterns leading to diagnostic difficulty. In this study of 257 patients, we aim to discuss the unusual sites of HCC metastasis, the various patterns of metastasis, clinicopathological features, and the most common cause of HCC in our population. In the course of our research study, we systematically extracted a comprehensive dataset comprising 257 instances of metastatic HCCs from the hospital database spanning the period from 2016 to February 2022. The assessment of metastatic sites uncovered a wide range of locations, reflecting significant diversity. The most common location was bone, with 135 cases (52.5%). The vertebral column was the most common location among bony metastasis, with 63 cases (24.7%). Morphologically, the most common histological pattern observed was pure trabecular in 192 patients (74.7%). All cases were diagnosed with the help of immunohistochemical stains. Out of 257 cases, 29.18% were diagnosed using glypican-3 and HepPar1, while 26.1% relied solely on HepPar1 positivity. HepPar1 was performed in a total of 240 cases, and positivity was seen in 205 cases (85.5%). In summary, our study represents the most comprehensive investigation of clinicopathological characteristics in metastatic HCC conducted within the past 20 years. It helps understand the histological and immunohistochemical features useful for diagnosis at metastatic sites for tumors with an unknown primary.

Delivery of extracellular vesicles loaded with immune checkpoint inhibitors for immunotherapeutic management of glioma

Glioma is a common primary malignant brain tumor with low survival rate. Immunotherapy with immune checkpoints inhibitors (ICI) can be a choice for glioma management, and extracellular vesicles (EVs) are recognized as a potential drug delivery system for various disease management due to their enhanced barrier permeation ability and immunomodulatory effect. The aim of this study is to develop ICI-loaded EVs (ICI/EV) that have sufficient efficacy in managing glioma. Calcium phosphate particles (CaP) were used to stimulate the secretion of EVs from murine macrophage cells. CaP conditioning of cells showed an enhanced amount of EVs secretion and macrophage polarization toward a proinflammatory phenotype. The CaP-induced EVs were shown to polarize macrophages into proinflammatory phenotype in vitro, as correlated with the conditioning method. ICI/EVs were successfully prepared with high loading efficiency using the sonication method. The EVs can be distributed throughout the entire brain upon intranasal administration and facilitate ICIs distribution into glioma lesion. Combinatory treatment with ICI/EVs showed benefit in glioma-bearing mice by reducing their tumor volume and prolonging their survival. Cytotoxic T cell infiltration, polarization of tumor-associated macrophage, and lower tumor proliferation were observed in ICI/EVs-treated mice. The developed ICI/EVs showed promise in immunotherapeutic management of glioma.

Updates for newly diagnosed and recurrent glioblastoma: a review of recent clinical trials.

Glioblastoma (GBM) is the most common and devastating primary malignant brain tumor. We summarize recent advances in radiotherapy, immunotherapy, and targeted therapy approaches for the treatment of newly diagnosed and recurrent glioblastoma. We also introduce ongoing clinical trials. Recent clinical trials have explored multiple novel strategies to treat GBM including the use of oncoviruses, chimeric antigen receptor (CAR) T cell therapy, vaccines, radiotherapy, and novel drug delivery techniques to improves drug penetrance across the blood brain barrier. Approaches to improve drug delivery to brain tumors have the potential to expand treatment options of existing therapies that otherwise have poor brain tumor penetrance. Immunotherapy has been of keen interest in both newly diagnosed and recurrent glioblastoma. Vaccines SurVaxM and DCVax-L have shown initial promise in phase II and III trials, respectively. CAR T cell therapy trials are in their early phases but hold promise in both newly diagnosed and recurrent glioblastoma. Although progress to improve outcomes for GBM patients has been modest, multiple novel strategies utilizing combination therapies, focused ultrasound to improve drug delivery, and novel immunotherapies are underway.

Induced membrane technique for malignant bone tumours of the humerus.

The aim of this study was to report on mid- to long-term results following large humeral tumoral resection and reconstruction with the induced-membrane technique in skeletally immature patients suffering from primary malignant bone tumours. A retrospective analysis identified all children who underwent the two stages of a humeral reconstruction using the induced-membrane technique for primary malignant humerus tumours between 2002 and 2020. Functional assessment was conducted by an independent observer using the Musculoskeletal Tumor Society (MSTS) scoring system for the upper limb. Radiological assessment was performed by two independent observers and the healing index was calculated (i.e., months/cm). Eight adolescents (5 osteosarcomas and 3 Ewing sarcoma), with a mean age of 14.2 years (SD = 2.7), were included. The mean length of the bone resection was 17.4cm (SD = 3.8), and the mean delay of the resection and reconstruction stages was 9.4 months (SD = 4). The mean follow-up was 6.6 years (SD = 4.3). The mean MSTS score was 77.4% and the global average healing index was 1.04 months/cm (SD = 2.2). Four complications (i.e., prominence device, fracture, aseptic pseudarthrosis, radial palsy) and one local recurrence were observed in four patients, requiring four unplanned surgical procedures in three patients. One patient died fourteen years after the initial treatment due to a lung recurrence. The induced-membrane technique is an effective and safe alternative for reconstructing large humeral bone defects after tumour resection in adolescents. Although this is a two-stage technique, it gives good functional results comparable to other strategies found in the literature. IV.

GAD1 ameliorates glioma progression through regulating cuproptosis via RAS/MAPK pathway.

Glioma represents a primary malignant tumor occurring in the central nervous system. Glutamate decarboxylase (GAD1) plays a significant role in tumor development; however, its function of GAD1 and underlying mechanisms in glioma progression remain unclear. Differentially expressed genes (DEGs) obtained from the GSE12657 and GSE15209 datasets that intersected with cuproptosis-related genes and pivot genes were identified using comprehensive bioinformatics methods. The elesclomol (ES) treatment was used to induce cuproptosis in U251 cells, which was validated by detecting intracellular copper levels and cuproptosis marker expression. Lentivirus-mediated gene overexpression was performed to explore the effects of GAD1 using functional assays in vitro and in a mouse xenograft model. The RAS agonist ML098 was used to verify the effect of GAD1 on the RAS/MAPK pathway in glioma cells. A total of 87 cuproptosis-related DEGs and seven hub genes were obtained, with five genes upregulated and two were downregulated in gliomas. Overexpression of GAD1 inhibited proliferation, invasion, and migration, promoted apoptosis of glioma cells, and suppressed tumorigenesis in vivo. In addition, GAD1 overexpression enhanced the sensitivity of glioma cells to cuproptosis. Additionally, ML098 treatment attenuated the inhibitory effect of GAD1 overexpression on the malignant phenotype of ES-treated cells. GAD1 plays an anti-oncogenic role in glioma by regulating apoptosis via inhibition of the RAS/MAPK pathway.

Managing malignant sublingual gland tumors: a single institution experience with 23 patients

BackgroundDue to the relative rarity of malignant sublingual gland tumors, diagnosing and treating them clinically pose challenges. Hence, there’s a need to explore the pathological types, characteristics, treatment methods, and prognosis of primary malignant tumors of the sublingual gland to improve our understanding and management of these rare yet highly malignant conditions.MethodsThis study reviewed cases of primary malignant sublingual gland tumors, analyzing their characteristics. The treatment methods included surgical excision, with additional radiotherapy, or brachytherapy for advanced stages or positive surgical margins. The study also summarized different treatment approaches, including lymph node dissection and soft tissue reconstruction using free flaps such as the anterolateral thigh flap and forearm flap.ResultsWe have gathered 23 cases of sublingual gland malignancies treated at the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, from January 2013 to May 2024. The most common pathological types were adenoid cystic carcinoma and mucoepidermoid carcinoma, with rare cases of mucosa-associated lymphoid tissue (MALT) lymphoma and nonspecific salivary gland clear cell carcinoma. Early diagnosis and surgical intervention were crucial for a favorable prognosis. Marginal mandibulectomy was necessary for cases involving the mandible. Patients with positive preoperative lymph node detection required cervical lymph node dissection. Extensive tissue defects in the floor of the mouth were effectively reconstructed with free flaps to prevent oral-mandibular fistula.ConclusionSurgical excision remains the preferred treatment for malignant sublingual gland tumors. Early diagnosis and comprehensive surgical management are essential for improving prognosis. The study’s limitations include a small sample size and short follow-up duration, necessitating further research with larger clinical samples to confirm these findings.

Analysis of High-Dose Ascorbate-Induced Cytotoxicity in Human Glioblastoma Cells and the Role of Dehydroascorbic Acid and Iron.

Several studies have demonstrated, both in vitro and in animal models, the anti-tumor efficacy of high-dose ascorbate treatment against a variety of tumor entities, including glioblastoma, the most common and aggressive primary malignant brain tumor. The aim of this study was to investigate the effects of high-dose ascorbate as well as dehydroascorbic acid on human glioblastoma cell lines and to evaluate different treatment conditions for the combined administration of ascorbate with magnesium (Mg2+) and iron (Fe3+). Intracellular levels of reactive oxygen species and the induction of cell death following ascorbate treatment were also investigated. We demonstrated high cytotoxicity and antiproliferative efficacy of high-dose ascorbate in human glioblastoma cells, whereas much weaker effects were observed for dehydroascorbic acid. Ascorbate-induced cell death was independent of apoptosis. Both the reduction in cell viability and the ascorbate-induced generation of intracellular reactive oxygen species could be significantly increased by incubating the cells with Fe3+ before ascorbate treatment. This work demonstrates, for the first time, an increase in ascorbate-induced intracellular ROS formation and cytotoxicity in human glioblastoma cells by pre-treatment of the tumor cells with ferric iron, as well as caspase-3 independence of cell death induced by high-dose ascorbate. Instead, the cell death mechanism caused by high-dose ascorbate in glioblastoma cells shows evidence of ferroptosis. The results of the present work provide insights into the efficacy and mode of action of pharmacological ascorbate for the therapy of glioblastoma, as well as indications for possible approaches to increase the effectiveness of ascorbate treatment.

Successful surgical treatment of metachronous carcinoma of the appulla of Vater and ductal carcinoma of the distal parts of the pancreas

Background. Currently, there is a steady trend towards an increase in the incidence of both synchronous and metachronous multiple primary malignant tumors (MPMT). However, metachronous polyneoplasia of the pancreatobiliary tract is relatively rare, and there have been very few reports on successful treatment of this malignancy. Case presentation. In September 2014, the patient K. was diagnosed with adenocarcinoma of the ampulla of Vater (T2N0M0, stage Ib) and underwent gastropancreatoduodenal resection with the creation of pancreatic-gastric anastomosis at the Abdominal Department of Cancer Research Institute of Tomsk National Research Medical Center. There were no complications in the postoperative period. At a 6.5-year followup, no evidence of disease progression was found. In April 2021, a follow-up examination conducted at the Cancer Research Institute revealed a large lesion on the distal part of the pancreatic stump with no clinically significant manifestations. Diagnosis of MPMT was confirmed by transgastric endoscopic ultrasound-guided biopsy. Histological and immunohistochemical examinations revealed undifferentiated ductal carcinoma of the pancreas. Considering the metachronous tumor localization, pancreatic stump extirpation with resection of the posterior wall of the stomach and splenectomy was performed. No complications occurred in the postoperative period. The patient received replacement therapy for exocrine pancreatic insufficiency and individual correction of carbohydrate metabolism. At a 15-month follow-up, liver metastases were detected, and palliative chemotherapy was administered. The patient died 6 months later due to disease progression. The survival time was 99 months after the first surgery and 21 months after the second surgery. Conclusion. We report a rare case of metachronous cancers of the ampulla of Vater and pancreatic stump developed with an interval of 6.5 years. The patient underwent successful curative resections consecutively. The overall survival time from the date of diagnosis was 99 months.

Causal Effect of Immunocytes, Plasma Metabolites, and Hepatocellular Carcinoma: A Bidirectional Two-Sample Mendelian Randomization Study and Mediation Analysis in East Asian Populations.

Background: Hepatocellular carcinoma (HCC) is a primary malignant liver tumor characterized by a low survival rate and high mortality. This study aimed to investigate the causal effect of immune cell phenotypes, plasma metabolites, and HCC in East Asian populations. Methods: The summary results for 731 immunocytes, 1400 plasma metabolites, and HCCs were acquired from publicly available genome-wide association studies (GWASs). This study utilized two-sample Mendelian randomization (MR) analysis to establish causal relationships, which was achieved by employing various statistical methods including inverse variance-weighted, simple mode, MR-Egger, weighted median, and weighted mode. Multiple sensitivity analyses were conducted to confirm the reliability of the MR data. Ultimately, mediation analysis was employed to ascertain the path that leads from immunocytes to plasma metabolites. Results: Among the 20 immune cells and HCC for East Asians, causal links were found, with one showing an inverse correlation. In addition, 36 metabolites were significantly associated with HCC for East Asians. Through analysis of established causative metabolites, we identified a strong correlation between the glycerophospholipid metabolic pathway and HCC for East Asians. By employing a two-step MR analysis, we identified 11 immunocytes that are causally linked to HCC for East Asians through the mediation of 14 plasma metabolites, with Linolenate [α or γ; (18:3n3 or 6)] levels showing the highest mediation proportion (19.3%). Conclusions: Our findings affirm the causal links among immunocytes, plasma metabolites, and HCC in eastern Asia populations by calculating the percentage of the impact that is influenced by plasma metabolites. This study offers innovative perspectives on the early detection, diagnosis, and therapy of HCC.

The causal relationship between CSF metabolites and GBM: a two-sample mendelian randomization analysis

BackgroundGlioblastoma multiforme (GBM) is a highly aggressive primary malignant brain tumor characterized by rapid progression, poor prognosis, and high mortality rates. Understanding the relationship between cerebrospinal fluid (CSF) metabolites and GBM is crucial for identifying potential biomarkers and pathways involved in the pathogenesis of this devastating disease.MethodsIn this study, Mendelian randomization (MR) analysis was employed to investigate the causal relationship between 338 CSF metabolites and GBM. The data for metabolites were obtained from a genome-wide association study summary dataset based on 291 individuals, and the GBM data was derived from FinnGen included 91 cases and 174,006 controls of European descent. The Inverse Variance Weighted method was utilized to estimate the causal effects. Supplementary comprehensive assessments of causal effects between CSF metabolites and GBM were conducted using MR-Egger regression, Weighted Median, Simple Mode, and Weighted Mode methods. Additionally, tests for heterogeneity and pleiotropy were performed.ResultsThrough MR analysis, a total of 12 identified metabolites and 2 with unknown chemical properties were found to have a causal relationship with GBM. 1-palmitoyl-2-stearoyl-gpc (16:0/18:0), 7-alpha-hydroxy-3-oxo-4-cholestenoate, Alpha-tocopherol, Behenoyl sphingomyelin (d18:1/22:0), Cysteinylglycine, Maleate, Uracil, Valine, X-12,101, X-12,104 and Butyrate (4:0) are associated with an increased risk of GBM. N1-methylinosine, Stachydrine and Succinylcarnitine (c4-dc) are associated with decreased GBM risk.ConclusionIn conclusion, this study sheds light on the intricate interplay between CSF metabolites and GBM, offering novel perspectives on disease mechanisms and potential treatment avenues. By elucidating the role of CSF metabolites in GBM pathogenesis, this research contributes to the advancement of diagnostic capabilities and targeted therapeutic interventions for this aggressive brain tumor. Further exploration of these findings may lead to improved management strategies and better outcomes for patients with GBM.

Comprehensive analysis of POLH-AS1 as a prognostic biomarker in hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC), a prevalent primary malignant tumor, is notorious for its high mortality rate. Despite advancements in HCC treatment, patient outcomes remain suboptimal. This study endeavors to assess the potential prognostic significance of POLH-AS1 in HCC.MethodsIn this research, we gathered RNA-Seq information from individuals with HCC in The Cancer Genome Atlas (TCGA). We analyzed the levels of POLH-AS1 expression in both HCC cells and tissues using statistical tests. Additionally, we examined various prognostic factors in HCC using advanced methodologies. Furthermore, we employed Spearman’s rank correlation analysis to examine the association between POLH-AS1 expression and the tumor’s immune microenvironment. Finally, the functional roles of POLH-AS1 in HCC were validated in two HCC cell lines (HEP3B and HEPG2).ResultsOur analysis revealed elevated POLH-AS1 expression across various cancers, including HCC, with heightened expression correlating with HCC progression. Notably, POLH-AS1 expression emerged as a potential biomarker for HCC patient survival and prognosis. Mechanistically, we identified the involvement of POLH-AS1 in tumorigenesis pathways such as herpes simplex virus 1 infection, interactions with neuroactive receptors, and the cAMP signaling pathway. Lastly, inhibition of POLH-AS1 was discovered to hinder the proliferation, invasion and migration of HEP3B and HEPG2 HCC cells.ConclusionsPOLH-AS1 emerges as a promising prognostic biomarker and therapeutic target for HCC, offering potential avenues for enhanced patient management and treatment strategies.

Patient-specific guides for consistently achieving R0 bone margins after resection of primary malignant bone tumors of the pelvis

AimsPrimary malignant bone tumor of the pelvis is an uncommon lesion, the resection of which via freehand osteotomy is subject to inaccuracy due to its three-dimensional anatomy. Patient-Specific Guides (PSG), also called Patient-Specific Instruments (PSI) are essential to ensure surgical planning and resection adequacy. Our aim was to assess their use and effectiveness.MethodsA monocentric retrospective study was conducted on 42 adult patients who underwent PSG-based resection of a primary malignant bone tumor of the pelvis. The primary outcome was the proportion of R0 bone margins. The secondary outcomes were the proportion of overall R0 margins, considering soft-tissue resection, the cumulative incidence of local recurrence, and the time of production for the guides. A comparison to a previous series at our institution was performed regarding histological margins.ResultsUsing PSGs, 100% R0 safe bone margin was achieved, and 88% overall R0 margin due to soft-tissue resection being contaminated, while the comparison to the previous series showed only 80% of R0 safe bone margin. The cumulative incidences of local recurrence were 10% (95% CI: 4–20%) at one year, 15% (95% CI: 6–27%) at two years, and 19% (95% CI: 8–33%) at five years. The median overall duration of the fabrication process of the guide was 35 days (Q1–Q3: 26–47) from the first contact to the surgery date.ConclusionsPatient-Specific Guides can provide a reproducible safe bony margin.

Single-cell analysis of breast cancer metastasis reveals epithelial-mesenchymal plasticity signatures associated with poor outcomes.

Metastasis is the leading cause of cancer-related deaths. It is unclear how intratumor heterogeneity (ITH) contributes to metastasis and how metastatic cells adapt to distant tissue environments. The study of these adaptations is challenged by the limited access to patient material and a lack of experimental models that appropriately recapitulate ITH. To investigate metastatic cell adaptations and the contribution of ITH to metastasis, we analyzed single-cell transcriptomes of matched primary tumors and metastases from patient-derived xenograft models of breast cancer. We found profound transcriptional differences between the primary tumor and metastatic cells. Primary tumors upregulated several metabolic genes, whereas motility pathway genes were upregulated in micrometastases, and stress response signaling was upregulated during progression. Additionally, we identified primary tumor gene signatures that were associated with increased metastatic potential and correlated with patient outcomes. Immune-regulatory control pathways were enriched in poorly metastatic primary tumors, whereas genes involved in epithelial-mesenchymal transition were upregulated in highly metastatic tumors. We found that ITH was dominated by epithelial-mesenchymal plasticity (EMP), which presented as a dynamic continuum with intermediate EMP cell states characterized by specific genes such as CRYAB and S100A2. Elevated expression of an intermediate EMP signature correlated with worse patient outcomes. Our findings identified inhibition of the intermediate EMP cell state as a potential therapeutic target to block metastasis.

Mapping the transcriptional evolution of human metastatic breast cancer.

Many aspects of breast cancer metastasis remain poorly understood, despite its clinical importance. In this issue of the JCI, Winkler et al. have applied an elegant patient-derived xenograft (PDX) model to map the transcriptomes of single cells in matched primary tumors and lung metastases across 13 breast cancer PDX models. They identified distinct transcriptional changes associated with metastatic evolution in lowly and highly metastatic primary tumors. Furthermore, by classifying the "epithelial-mesenchymal plasticity" (EMP) state of single cells, they revealed that considerable EMP heterogeneity exists among primary and metastatic human breast cancer cells. However, the EMP profile of a tumor does not change substantially upon metastasis. These findings give an unprecedentedly detailed view into the transcriptional heterogeneity and evolution of metastatic human breast cancer.

High-quality expert annotations enhance artificial intelligence model accuracy for osteosarcoma X-ray diagnosis.

Primary malignant bone tumors, such as osteosarcoma, significantly affect the pediatric and young adult populations, necessitating early diagnosis for effective treatment. This study developed a high-performance artificial intelligence (AI) model to detect osteosarcoma from X-ray images using highly accurate annotated data to improve diagnostic accuracy at initial consultations. Traditional models trained on unannotated data have shown limited success, with sensitivities of approximately 60%-70%. In contrast, our model used a data-centric approach with annotations from an experienced oncologist, achieving a sensitivity of 95.52%, specificity of 96.21%, and an area under the curve of 0.989. The model was trained using 468 X-ray images from 31 osteosarcoma cases and 378 normal knee images with a strategy to maximize diversity in the training and validation sets. It was evaluated using an independent dataset of 268 osteosarcoma and 554 normal knee images to ensure generalizability. By applying the U-net architecture and advanced image processing techniques such as renormalization and affine transformations, our AI model outperforms existing models, reducing missed diagnoses and enhancing patient outcomes by facilitating earlier treatment. This study highlights the importance of high-quality training data and advocates a shift towards data-centric AI development in medical imaging. These insights can be extended to other rare cancers and diseases, underscoring the potential of AI in transforming diagnostic processes in oncology. The integration of this AI model into clinical workflows could support physicians in early osteosarcoma detection, thereby improving diagnostic accuracy and patient care.

Clinical and Prognostic Characteristics in Childhood Osteosarcoma: A Single-Center Experience in Türkiye.

In our study, we aimed to share the clinical experiences of our center regarding osteosarcoma cases, the most common primary malignant bone tumor in children and adolescents. With approval from the Clinical Research Ethics Committee of our center, the data of 59 pediatric patients who were followed up in our center with the diagnosis of osteosarcoma between 2007 and 2021 were evaluated retrospectively. The mean time between the onset of symptoms and diagnosis was 3 months. Although not statistically significant, patients with a diagnostic delay of 3 months or less had a higher rate of recurrence and mortality. 59.3% of patients had metastatic disease, and the presence of metastases was associated with higher rates of recurrence and mortality. Significant number of patients had multiple surgical operations. Amputation as the first operation and the need for multiple surgeries were associated with higher mortality. Pathologically poor response to chemotherapy is associated with mortality. 42.4% of patients died, and the 5-year overall and disease-free survival rates were 47.5% and 30.5%, respectively. Survival rates were highest in non-metastatic and non-relapsed patients, and lowest in metastatic patients and patients with poor response to chemotherapy. Renal problems and cardiotoxicity were most frequently treatment-related complications. Significant improvements have been achieved in the survival and quality of life in osteosarcoma cases compared to previous years; however, there is still a long way to go, and more multicenter and multidisciplinary studies are needed on osteosarcoma.

Prediction of early recurrence of adult-type diffuse gliomas following radiotherapy using multi-modal magnetic resonance images.

Adult-type diffuse gliomas are among the central nervous system's most aggressive malignant primary neoplasms. Despite advancements in systemic therapies and technological improvements in radiation oncology treatment delivery, the survival outcome for these patients remains poor. Fast and accurate assessment of tumor response to oncologic treatments is crucial, as it can enable the early detection of recurrent or refractory gliomas, thereby allowing timely intervention with life-prolonging salvage therapies. Radiomics is a developing field with great potential to improve medical image interpretation. This study aims to apply a radiomics-based predictive model for classifying response to radiotherapy within the first 3 months post-treatment. Ninety-five patients were selected from the Burdenko Glioblastoma Progression Dataset. Tumor regions were delineated in the axial plane on contrast-enhanced T1(CE T1W) and T2 fluid-attenuated inversion recovery (T2_FLAIR) magnetic resonance imaging (MRI). Hand-crafted radiomic (HCR) features, including first- and second-order features, were extracted using PyRadiomics (3.7.6) in Python (3.10). Then, recursive feature elimination with a random forest (RF) classifier was applied for feature dimensionality reduction. RF and support vector machine (SVM) classifiers were built to predict treatment outcomes using the selected features. Leave-one-out cross-validation was employed to tune hyperparameters and evaluate the models. For each segmented target, 186 HCR features were extracted from the MRI sequence. Using the top-ranked radiomic features from a combination of CE T1W and T2_FLAIR, an optimized classifier achieved the highest averaged area under the curve (AUC) of 0.829±0.075 using the RF classifier. The HCR features of CE T1W produced the worst outcomes among all models (0.603±0.024 and 0.615±0.075 for RF and SVM classifiers, respectively). We developed and evaluated a radiomics-based predictive model for early tumor response to radiotherapy, demonstrating excellent performance supported by high AUC values. This model, harnessing radiomic features from multi-modal MRI, showed superior predictive performance compared to single-modal MRI approaches. These results underscore the potential of radiomics in clinical decision support for this disease process.

Establishment of a nomogram for potential prediction of lung metastasis in patients with primary limb bone tumors: a study based on the SEER database.

The prognosis of lung metastasis in primary limb bone tumors represents a pivotal yet challenging aspect of oncological management. Despite advancements in diagnostic modalities, the predictive accuracy for metastatic spread remains suboptimal. This study aims to bridge this gap by leveraging the Surveillance, Epidemiology, and End Results (SEER) database to construct a nomogram that forecasts the risk of lung metastasis, thereby enhancing clinical decision-making processes. A retrospective cohort, including 1,822 patients with primary limb bony tumors from 2010 to 2015 in the SEER database, was extracted. Using precise inclusion and exclusion criteria, variables essential for predicting lung metastasis were identified through univariate and multivariate analyses, along with least absolute shrinkage and selection operator (LASSO) regression. These variables provided a solid basis for creating the multivariable nomogram, of which the discriminating power and utility were verified using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis. The model incorporated seven key predicting variables, including age, histological type, surgery, radiation, chemotherapy, T stage, and N stage. The nomogram emerged as a cohesive whole with good discriminative power. The area under the curve (AUC) was 0.806 in the training cohort and 0.767 in the validation cohort. The calibration curves demonstrated the model's validity by showing a good match between the actual outcomes and the model-predicted probabilities of lung metastasis. This study showed for the first time the reliability of the predictive model in translating the hard-to-interpret demographic, clinical, and pathologic data into a very usable predictive model. Thus, it represents a significant step toward demystifying the risk of lung metastasis in primary limb bone tumors. It is an invitation for a paradigm shift of oncology, to evidence-based, person-based oncology that is taking a new metric for cancer prognosis.